The with the cleavage of ortho-hydroxylated aromatic Mannich bases to yield methylated products of relatively high purity using only moderate reaction conditions.
The ortho-hydroxylated aromatic Mannich bases derived from dimethylamine were stable under catalytic hydrogenation conditions, whereas the corresponding morpholino derivatives were able to achieve hydrogenolysis. P. N. Rylander reported this in "Catalytic Hydrogenation Over Platinum Metals", Academic Press (1967) at page 467. Green et al, in U.S. Pat. No. 3,187,049 (1965) showed that when the Mannich base has a nitro group meta to the aminomethyl group, the nitro group can be reduced and the dimethylamino group of the hydrochloride salt can be cleaved to give the methyl group in one operation using 33% by weight of 10% Pd on barium sulfate (3.3% Pd by weight) as catalyst. The absence of intramolecular hydrogen bonding in the hydrochloride salt was responsible for the ease of hydrogenolysis of the dimethylamino group. The poor reactivity of ortho-phenolic Mannich bases was discussed by M. Tramontini in "Advances in the Chemistry of Mannich Bases", Synthesis, volume 703 (1973), at page 750.
In U.S. Pat. No. 3,461,172, Previc disclosed the hydrogenation of ortho-phenolic Mannich bases via the steps of (1) conversion of the base to its hydrochloride salt and (2) hydrogenation of the salt using an acid resistant catalyst at 100 to 3,000 psi hydrogen pressure and 125.degree. to 225.degree. C.
R. Borchardt et al reported in J. Org. Chem., 46 (1981), pp. 5021-2 that a 70% yield of 3,5.-dihydroxy-4-methylbenzoic acid could be obtained from 2,6-dibromo-3,5-dihydroxy-4-[(N,N-dimethylamino)methyl]benzoic acid by treatment with 3N sodium hydroxide in an equal weight of Raney nickel alloy at 25.degree.-30.degree. C.
U.S. Pat. Nos. 3,946,086; 4,117,244; 4,215,229; and 4,480,140 disclose the hydrogenation of Mannich bases at temperatures above 80.degree. C.
U.S. Pat. No. 4,475,001 discloses a process for producing ortho-alkylated phenols from phenols via the steps of (1) making a tertiary alkylated phenol, (2) making a Mannich base from the product of (1) while retaining the t-alkyl group, (3) removing the t-alkyl group, and (4) hydrogenating the Mannich base at 0.degree. to 175.degree. C. This synthesis, like that of Previc, involves the use of an intermediate.